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So nice to know I'm not the only paranoid one. :-) But sad to know that sometimes "just because you're paranoid, doesn't mean their not after you". :-(
**Off to go check prices for tiny cam. . .Read More

The Journal of Neuroscience Table of Contents arrived in my inbox last week, and like I do on most such occasions, I browsed it for research in my area and people I know. Very often I see papers that strike my fancy, but for some reason, when I saw this article, I really wanted to...talk about it. Or blog about it, I suppose. So without further ado, I bring you my very first Research Blogging post.

Dendritic Growth in Medial Prefrontal Cortex and Cognitive Flexibility Are Enhanced during the Postpartum Period J Neurosci. 2010; 30 13499-13503

Benedetta Leuner and Elizabeth Gould

If we were playing a game of word association, and the word I gave you was "postpartum," chances are you'd come up with "depression," am I right? It's totally natural. Postpartum Depression (PPD) is a well-known disorder that affects somewhere around 10% of women who give birth, and whose symptoms are similar to that of Major Depressive Disorder--feelings of sadness, hopelessness, lethargy, and disrupted sleep and appetite, to name but a few. While these kinds of symptoms are clearly not good for anyone, they're especially bad for new moms, who really need to be on their game in order to adequately take care of a newborn. It's generally thought that PPD results at least in part because of the large fluctuations in hormones that a woman's body undergoes right after she gives birth, but not a lot of work has been done in postpartum animals to really find out what's going on in brain areas commonly associated with depression.

One of the major hormonal changes the postpartum body undergoes is a sustained increase in glucocorticoids. Glucocorticoids are primarily thought of as stress hormones, as they're released during stress and can help bring your body and brain back to normal states after you're done with all that fight-or-flight business. However, too much exposure to glucocorticoids can be a bad thing, and many models of chronic stress involve subjecting animals to repeated glucocorticoids. This has been shown to cause changes in neuronal morphology in two major brain areas associated with depression--the prefrontal cortex (PFC) and the hippocampus. In male rats, prolonged glucocorticoid exposure can lead to reduced spine density in these regions, which theoretically could mean less opportunity for these neurons to connect to other neurons. Animals exposed to glucocorticoids also are impaired on some cognitive tasks that we know are governed by the PFC and hippocampus, and thus the general dogma is: high glucocorticoids---> fewer spines---> impaired brain. It's much more complicated than that, but this'll do for my purposes here.

So the authors of this paper thought, OK, the postpartum brain is just swimming in glucocorticoids, so maybe the glucocorticoids are causing spine loss and thus the PFC isn't functioning properly, and that's why women get PPD! They tested their hypothesis by comparing postpartum and virgin female rats' performance in a cognitive task known to require an optimally-functioning PFC called attentional set-shifting, and then looked at the rats' spine density in the PFC. They thought that the postpartum animals would be impaired at the task and have fewer spines when compared to the virgins, but in fact, things went in the complete opposite direction! The postpartum dams had greater spine density in the PFC and did better on the attentional set-shifting task then the virgin females. Counter-intuitive, no?

No!! The authors re-evaluated what their results meant in the context of PPD, and I like what they came up with. When you think about it, most women don't develop PPD after giving birth; in fact, most do a pretty good job of taking care of their babies, which it's my understanding is no small feat! It requires being able to nimbly switch your attention between tasks, and make decisions about what's the most important thing at any particular time--activities mediated by the PFC. The authors think their findings may mean that under normal circumstances, the brain responds to giving birth by increasing spines and ramping up PFC function, which could help women better deal with the multi-tasking the postpartum period requires. Perhaps, then, women in whom this response fails to happen are the ones who develop PPD--they're lacking the natural adaptation that the brain needs in order to successfully handle early motherhood.

It's difficult to study psychiatric illnesses in animals, not only because these are very complex--and often very human--disorders, but because they're relatively rare. If only 10% of the population is afflicted with a given affective disorder, what are the chances that your n=12 rats are going to be in any way representative of that 10%? Pretty slim, I'd say. What I think researchers are now understanding better is that if we want to learn about the pathophysiology of mental illness from animals, the most valuable insights are going to come from looking closely at the extreme ends of the response spectrum, rather than the norms.

Leuner B, & Gould E (2010). Dendritic Growth in Medial Prefrontal Cortex and Cognitive Flexibility Are Enhanced during the Postpartum Period. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (40), 13499-503 PMID: 20926675

Interesting report. Good summary. My friend had terrible PPD after her kids were born, and it was pretty scary for a while. I didn't realize that the percentage of affliction was so low though. I would have expected higher than 10%.

I like this post a lot, Becca, especially since the paper itself might have scared off the microbiologist in me. ;) I'm intrigued by their rat findings, especially considering the fact that PPD usually strikes several weeks (I think 2-3) after birth. I've also heard multiple studies have shown new moms are able to achieve quite the feats of brainpower, especially considering their levels of exhaustion; it'll be interesting to see how/when the PFC activity gets ramped up during this time period, and how this translates to humans.

Nikkilina - there are much higher levels (50-80%) of what's referred to as "postpartum blues", a milder form that usually only lasts a few days, before mom "snaps" out of it, and generally doesn't require treatment. The doctors are telling us to look out for symptoms lasting longer than a week and/or past the first couple of weeks after giving birth when looking out for true depression.

Interesting article. I'd be very cautious correlating what happens in rats to what happens in humans. Rat pup wean at around 3 weeks. For humans, its generally much longer. Based on my wife's experience, its the nursing that takes its toll on the new mom. Our oldest wanted to eat every 2 - 3 hours and was exhausting. Now throw on top of this our modern desire to be super parents and its no wonder severe depression can set in. I'm wondering if any research has been done on correlation between PPD and parenting styles. For instance, do moms who switch to bottle feeding and formula early have less PPD than hard-core nursing moms?

John, I have a couple of answers for you. First, there is a slightly increased risk factor for PPD in moms who use formula, rather than breast feed. Along those lines, the authors speculate that the process of nursing in the animals might contribute to the increases in spine density that they observed, since spines can change with activity, and it's been shown that contact with offspring can increase neuronal activity in the PFC.

Your points about translating from rat to human are of course very well taken. I wouldn't necessarily see time as one of the biggest confounding factors, though--remember, a rat's life is only about 2 years long, so 3 weeks in a rat life is in fact comparable to much longer in a human. And to get at one of Dr. O's points, the behavioral studies started on post-natal day 11 for the dams, so they were a little ways out from the birth itself.

Great post! I enjoy reading the articles that pose a logical hypothesis, then find that the results show "Whoops! Totally opposite," and then end with another logical counter argument. I tend to not be overly critical of rat models, we have to start somewhere, and yes it's obvious that there are dissimilarities between the populations and cautionary issues to acknowlege. It will be interesting to see how, or if, this replicates. (Then again, no agencies like to hand out money for simple replication studies now do they? That wouldn't be novel enough, or "translative" enough... it would only be good, solid science. No one's interested in that, right?)

I don't know if they vet n00bs before letting you in to the club, but I know there was some discussion over there recently about making folks more aware of the "rules". Drop jason a line, or get in touch with RB directly... Dave Munger is on Twitter @davemunger

Don't worry yet. I'm sure the admins just haven't gotten to it - if its not through by the end of the day, its worth checking in. There is some vetting, mostly to make sure that the blogs that apply are legitimate science blogs and not full of pseudoscientific wackaloonery. Scientific wackaloonery totally acceptable, of course.

This is a fantastic first research blog, incredibly well summarised and captivating! Fabulous! Really interesting topic and finding as well. In regards to the nursing versus bottle feeding, I wonder if the 'breast is best' pressure might also contribute to this, the pressure to be the best parent as someone also picked up, maybe the perceived 'failure' at breast feeding might add to the PPD feelings.

Are people who are naturally susceptible to other types of depression also more susceptible to PPD, is there any correlation there?

I think there is an increased risk for PPD if you have a history of MDD, yes. What outside psychological factors can contribute I think have not been completely figured out--or rather, it's different for everyone. But what I like about this paper is that it suggests that developing PPD may not have to do with whether you've got XYZ stresses as part of your new mom-ness, but whether your brain has adequately prepared you to deal with those stresses.

Interesting. Subjectively, of course, attention problems and stereotypical PFC self-control problems can result directly from sleeping problems (caused by either a newborn or MDD). So it *seems* like it's whether your brain is adequately responding to new stresses, rather than your brain changing first in a fashion that may or may not prove to be adequate. But I'm pretty sure there's a general feed forward cycle here somewhere.

Is there any evidence that spine density in the PFC might, for a normal person, be impaired by lack of sleep and high glucocorticoid levels, but that that situation is reversed during the postpartum period?

And I can't help but wonder- is there any way to specifically model PPD in rats? I mean, I don't know that it's ethical, but if you stress the heck out of the rats can you get them to disengage from their pups? I could be wrong here, but I think that viewing PPD as a discrete thing from baby blues is probably misleading. I think it's a difference in degree, not in type. I suspect if you put the rats in the right circumstances (or gave them cortisol + oxytocin blockers, or something), you could induce PPD-like behaviors in the bulk of the population.

And becca, I was just talking to Sci about this very idea! I don't think there is an official model of PPD, but there are plenty of dams that will ignore their pups without any manipulations by experimenters. The focus in these cases is usually on what happens to the neglected pups when they grow up, but it would be super interesting to look at the moms as well.